Orlistat Inhibits Dietary Cholesterol Absorption

Objective: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low‐density lipoprotein‐cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. Research Methods and Procedures: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m 2 ) by simultaneous administration of intravenous ([ 2 H 6 ] cholesterol) and oral ([ 2 H 5 ] cholesterol) cholesterol tracers. In protocol 1 ( n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 ( n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. Results: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 ± 5% and 51 ± 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 ± 6% to 44 ± 5% ( p < 0.01). Discussion: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.